Summary of work: Alzheimers disease (AD) is the most widespread among several neurological degenerative diseases (dementias) that occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimers disease follow the NINCDS-ADRDA criteria. Estrogen replacement therapy (ERT) is increasingly recommended for post-menopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk for Alzheimers disease. We tested whether ERT had a protective effect on memory in nondemented women from the Baltimore Longitudinal Study of Aging. Study groups included 103 active users of oral or transdermal ERT and 81 never-users who were free of dementia up to 5 years after assessment. Groups were matched on education, health status, depressive symptoms, annual income, and general verbal ability. Data were cross-sectional. ERT users showed significantly better verbal learning and memory than never-users on several measures of the California Verbal Learning Test, p < .05, but not on tests of figural memory, mental rotations, attention or working memory. ERT use was associated with enhanced encoding and retrieval of verbal information, and less sensitivity to interference during memory performance. Memory performance did not vary with duration of use nor with concurrent progesterone use. Data suggest a significant and selective effect of ERT on memory. These findings indicate the need for longitudinal studies to determine whether ERT use protects against age- related memory decline in nondemented women.High concentrations of dehydroepiandrosterone (DHEA) may prevent or reverse normal age-related declines in memory and cognitive function. DHEA is widely available in the United States as an over-the-counter supplement that elderly individuals are self-prescribing to impede age-related cognitive, as well as physical change. In this study, we investigated the relationship between declines in endogenous DHEA concentrations and declines in cognitive performance. Subjects were participants in the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample aged 22 to 91 years at initial visit in which 883 men were followed up to 31 years (mean = 11.55 years) with biennial reassessments of multiple cognitive domains and contemporaneous plasma DHEA. Cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency, and measures of visuomotor scanning and attention. Plasma DHEA concentrations were determined by standard radioimmunoassay. Neither the rate of decline in DHEA nor the within-individual mean DHEA concentrations were related to cognitive status or cognitive decline. An extreme-groups comparison between the highest and lowest DHEA quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA concentration by more than a factor of 4 for an average duration of 12 years. Our longitudinal results are consistent with previous cross- sectional studies suggesting that endogenous decline in DHEA is independent of cognitive status and cognitive decline in healthy aging. - cognitive ability, cognitive impairment, Alzheimer's disease - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only